Real-World Data Analysis Highlight Clinical Profiles and Inebilizumab Use Patterns in NMOSD

A newly presented real-world analysis of the SPHERES registry (NCT04886492) showed that patients with neuromyelitis optica spectrum disorder (NMOSD) treated with inebilizumab (Uplizna; Amgen) commonly had prior relapses, moderate disability, and high rates of aquaporin-4 antibody seropositivity (AQP4-IgG+), with the therapy used across multiple lines of treatment in clinical practice.¹

Among 422 registry patients prescribed therapy for NMOSD, researchers assessed 68 who received inebilizumab. Presented at the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 5-7, in San Diego, California, a majority of the patients included were AQP4-IgG+ (93%). Prior to the index visit, patients had experienced a substantial relapse burden, with 32% reporting 1 prior relapse, 19% reporting 2 relapses, and nearly half experiencing 3 or more relapses (49%). Notably, investigators reported that the mean number of prior relapses was 3.2 (SD, 2.6).

“The objective of this study was to evaluate clinical characteristics and treatment patterns associated with inebilizumab use in a real-world clinical setting,” lead author Michael Levy, MD, PhD, associate professor of neurology at Massachusetts General Hospital, and colleagues wrote.¹ “This descriptive analysis of real-world NMOSD patients who were treated with inebilizumab offers important insights into clinical characteristics and treatment patterns. Additional analysis is being conducted to understand inebilizumab treatment persistence and long-term patient outcomes.”

The analysis included adult patients aged 18 years or older who were enrolled in the US-based SPHERES (Synergy of Prospective Health & Experimental Research for Emerging Solutions) Registry between June 2, 2021, and February 28, 2025. All patients had a diagnosis of NMOSD according to the 2015 International Panel for NMO Diagnosis criteria.² The index visit was defined as either the registry enrollment visit for patients who initiated inebilizumab prior to joining SPHERES or the visit corresponding to treatment initiation for those who began inebilizumab at or after enrollment.

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In the analysis, researchers observed that measures of disease activity and patient-reported outcomes at the index visit suggested moderate disease burden. The mean expanded disability status scale score was 3.5 (SD, 1.9), indicating ambulatory impairment in some patients. Health-related quality of life, assessed using the 5-level EQ-5D, showed a mean score of 0.7 (SD, 0.3), while the mean EQ visual analogue scale score was 70.6 (SD, 18.9). Additional results revealed that cognitive performance, as measured by the Montreal Cognitive Assessment Blind, was in the normal range for 71% of patients.

Treatment sequencing varied across the cohort. Inebilizumab was used as first-line therapy in 47% of patients, while 35% received it as second-line therapy. Smaller proportions received inebilizumab as third-line (12%) or fourth-line or later therapy (6%). Among patients who initiated inebilizumab as second-line treatment, prior therapies included rituximab in 14 patients, satralizumab in 3 patients, nonapproved biologics in 2 patients, glucocorticoid steroids in 3 patients, immunosuppressant therapy in 1 patient, and immunoglobulin therapy in 1 patient.

Inebilizumab is a humanized, monoclonal antibody designed to bind with high affinity to CD19 and deplete a broad range of B cells. The FDA approved the treatment for adults with AQP4 antibody positive NMOSD in June 2020, supported by data from the N-MOmentum study (NCT02200770).³ The trial included 231 patients with NMOSD who were randomly assigned to receive either 2 intravenous doses of inebilizumab monotherapy or placebo for a 6.5-month treatment period. In the N-MOmentum trial, findings showed that the risk of NMOSD relapse was reduced by 77% in the treatment group compared with placebo in participants.

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REFERENCES
1. Levy M, Cavida D, Patterson KR, et al. Inebilizumab for treatment of NMOSD in a Real-World Cohort: Analysis from the SPHERES Registry. Presented at ACTRIMS Forum 2026; February 5-7; San Diego, California. P432.
2. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:10.1212/WNL.0000000000001729
3. FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord. News release. FDA. June 11, 2020. Accessed February 5, 2026. https://www.prnewswire.com/news-releases/fda-approves-new-therapy-for-rare-disease-affecting-optic-nerve-spinal-cord-301074820.html